c-Abl Tyrosine Kinase Is Not Essential for Ataxia Telangiectasia Mutated Functions in Chromosomal Maintenance

c-Abl is activated by DNA damage in an ataxia telangiectasia mutated (ATM)-dependent manner and plays important roles in growth arrest and apoptosis induced by DNA damage. c-Abl also interacts physically and functionally with Rad51, a key molecule in homologous recombinational (HR) DNA repair. To study further the roles of c-Abl in HR DNA repair, we generated c-Abl−/− andATM−/−/c-Abl−/−mutant cell lines from a chicken B lymphocyte DT40 cell line, comparing the phenotypes of these mutants to those ofATM−/− DT40 cells that we had created previously. We found that the time course of radiation-induced Rad51 focus formation is abnormal in ATM−/− DT40 cells, consistent with the observation thatATM−/− DT40 cells display hypersensitivity to ionizing radiation and highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In contrast, c-Abl−/− cells did not show these ATM-related defects in their cellular response to radiation, nor did the disruption of c-Abl in ATM−/−DT40 cells exacerbate these ATM-related defects. However,c-Abl−/− DT40 cells, but not ATM−/− DT40 cells, were resistant to radiation-induced apoptosis, indicating an important role for c-Abl in this cellular response to ionizing radiation. These results therefore indicate that, although ATM plays an important role in genome maintenance, c-Abl is not essential for this ATM function. These findings suggest that c-Abl and ATM play important roles in the maintenance of the cell homeostasis in response to DNA damage that are, at least in part, independent.